Toxicology of Industrial Compounds

Figure 20.2 Cycle of life/reproduction.
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OECD 421 involves treatment of both sexes from about 2 weeks prior to
mating through to termination, a few days after birth of offspring
(Figure 20.3). Assessment of male fertility is achieved in two parts. Males
are paired with females for detection of effects unrelated to
spermatogenesis, for example, effects on sexual behaviour, libido or
ejaculation and functional maturation of sperm.
For detecting effects on spermatogenesis, direct methods, particularly
histopathological examinations of testes and epididymides are used. Sperm
analysis (seminology) could be added, although it does not seem to be
better than histopathology. These methods could be incorporated into
systemic toxicity studies rather than in the reproduction study per se.
In respect of fecundity, treatment and observations of females include
most of those applied in full scale tests. An exception is the lack of
observations for delayed, post-natal manifestations. Detailed examination
of foetuses for skeletal and soft tissue abnormalities is not included. The
potential for prenatal effects is deduced by observation of post-natal
differences in numbers pregnant, litter size, litter and mean pup weight at
birth and to day 4 post partum.
As with any guideline, OECD 421 should be used with commonsense
and flexibility. If pretesting prognosis suggests that prenatal effects are
unlikely, extension of the study to weaning of the offspring (Figure 20.3)
provides added safeguards at little extra cost. Increase group size and it